No abstract uploaded!

Adult stem cells, which exist throughout the body, multiply by cell division to replenish dying cells or to promote regeneration to repair damaged tissues. To perform these functions during the lifetime of organs or tissues, stem cells need to maintain their populations in a faithful distribution of their epigenetic states, which are suscepti- ble to stochastic fluctuations during each cell division, unexpected injury, and potential genetic mutations that occur during many cell divisions. However, it remains unclear how the three processes of differentiation, proliferation, and apoptosis in regulating stem cells collectively manage these challenging tasks. Here, without consid- ering molecular details, we propose a genetic optimal control model for adult stem cell regeneration that includes the three fundamental processes, along with cell division and adaptation based on differ- ential fitnesses of phenotypes. In the model, stem cells with a distri- bution of epigenetic states are required to maximize expected performance after each cell division. We show that heteroge- neous proliferation that depends on the epigenetic states of stem cells can improve the maintenance of stem cell distributions to create balanced populations. A control strategy during each cell division leads to a feedback mechanism involving heterogeneous proliferation that can accelerate regeneration with less fluctuation in the stem cell population. When mutation is allowed, apoptosis evolves to maximize the performance during homeostasis after multiple cell divisions. The overall results highlight the importance of cross-talk between genetic and epigenetic regulation and the performance objectives during homeostasis in shaping a desirable heterogeneous distribution of stem cells in epigenetic states.

For spacetimes that are not asymptotic to anti-de Sitter Space (non AAdS), we adapt the Lewkowycz-Maldacena procedure to find the holographic entanglement entropy. The key observation, which to our knowledge is not very well appreciated, is that asymptotic boundary conditions play an essential role on extending the replica trick to the bulk. For non AAdS, we expect the following three main modifications: (1) the expansion near the special surface has to be compatible with the asymptotic expansion; (2) periodic conditions are imposed to coordinates on the phase space with diagonalized symplectic structure, not to all fields appearing in the action; (3) evaluating the entanglement functional using the boundary term method amounts to evaluating the presymplectic structure at the special surface, where some additional exact form may contribute. An explicit calculation is carried out for three-dimensional warped anti-de Sitter spacetime (WAdS3) in a consistent truncation of string theory, the so-called S-dual dipole theory. It turns out that the generalized gravitational entropy in WAdS3 is captured by the least action of a charged particle in WAdS3 space, or equivalently, by the geodesic length in an auxiliary AdS3. Consequently, the bulk calculation agrees with the CFT results, providing another piece of evidence for the WAdS3/CFT2 correspondence.

No abstract uploaded!

No abstract uploaded!